An increasing number of microsystems have been presented during the last decade. The main focus of microscaling has been the analytical and/or preparative performance of these microsystems and in practice very little attention has been paid on interfacing these microworlds with the surrounding macroworld. The present invention presents an interfacing solution and concerns dispensation of liquid to microsystems comprising one, two or more target areas.
Previous microfluidic systems have typically comprised one, two or more microchannel structures in which liquids are transported and processed. Variants that can be spun around an axis of symmetry for driving liquid flow within the structures have been suggested previously, e.g. circular forms and other kinds discs having an axis of symmetry.
Modifications of traditional ink-jet technology have been suggested to accomplish liquid dispensation to target areas in microsystems. In most cases the dispensing unit has been linked to a liquid reservoir (Sziele at al., “Adaption of a microdrop injector to sampling in capillary electrophoresis”, J. Chromatogr. A 669 (1994) 254-257; Schober et al., “Accurate high-speed liquid handling of very small biological samples”, Biotechniques 15 (1993) 2; Nilsson et al., “Thin-layer immunoaffinity chromatography with bar code quantitation of C-reactive protein”, Anal. Chem. 67 (1995) 3051-3056; Wallace et al., “Ink-jet based fluid microdispensing in biochemical applications”, Lab. Automation News 1(5) (1996) 6-9; and Lemmo et al., “Characterization of an inkjet chemical microdispenser for combinatorial library synthesis” Anal. Chem. 69 (1997) 543-551). Some years ago a versatile through-flow channel microdispenser that could be adapted for dispensation to microsystems was presented (Laurell et al., “Flow-through sampling cell and use thereof” U.S. Pat. No. 6,192,768, Gyros AB) and later further developed (Laurell et al., “Design and development of a silicon microfabricated flow-through dispenser for on-line picoliter sample handling”, J. Micromech. Microeng. 9 (1999) 369-376; Thornell et al., “Desk top microfabrication—Initial experiments with a piezoceramic”, 9 (199) 434-437; Tormod et al., “Device for dispensing droplets”, WO 0130500, Gyros AB and Stjernström et al., “A multi-nozzle piezoelectric microdispenser for improving the dynamic volumetric range of droplets” in Proceedings of μ-TAS 2000 Symposium 14-18 May, 2000, Enschede, the Netherlands, Eds. van den Berg et al., Kluwer Academic Publisher).
The flow-through sampling cell developed by Laurell et al (supra) has been suggested for dispensing droplets to microfludic discs (Ekstrand et al., “Microfluidics in a rotating CD” in Proceedings of μ-TAS 2000 Symposium 14-18 May, 2000, Enschede, the Netherlands, Eds van den Berg et al., Kluwer Academic Publisher).
Previously liquid aliquots in the microliter (μl) range have been dispensed to individual target areas of resting discs. Spinning (centrifugal force) has been used to control the motion of the liquid into and within the structures. This dispensation procedure is tedious and suffers from a number of drawbacks, in particular if dozens of microstructures have to be fed before spinning. Many of the drawbacks become more accentuated when going down to dispensation of nl- and pl-volumes.
Dispensation while spinning a microsystem has the potential of feeding large numbers of target areas at the same time solving the problem of interconnecting hundreds of target areas. Interconnecting is tedious and has not yet been achieved in standard microfabrication procedures (Ellis Meng et al., “Micromachined fluidic couplers” and Aniruddha Puntambekar et al., “Self-aligning microfluidic interconnects with low dead volume” in Proceedings of μ-TAS 2000 Symposium 14-18 May, 2000, Enschede, the Netherlands, Eds van den Berg et al., Kluwer Academic Publisher).
Dispensation of liquid aliquots during spinning is associated with targeting problems that are not at hand when the disc is resting because during spinning the target area is moving.
Dispensation of droplets to a spinning microfluidic disc has been presented in a poster after the priority date of the present invention. See Jesson & Andersson “Multiple separations at nanoliter scale using gradient elution” in Proceedings of μ-TAS 2001 Symposium, Oct. 21-25, 2001, Monterey, USA, Eds. Ramsey and Van der Berg (20001) Kluwer Academic Publisher. The poster can be downloaded from w.w.w.gyros.com.